The objective of this project is to evaluate the relationship between tumor growth, opsonin levels, and the phagocytic activity of the reticuloendothelial (R.E.) system. Macrophage function has been suggested to be a major host defense mechanism against cancer. Furthermore, opsonins are a major physiologic factor regulating macrophage phagocytosis. These findings suggest that failure of the macrophage mediated host defense mechanism against neoplasia may, in part, be due to a deficiency of opsonins. If an opsonin deficit mediates impaired macrophage anti-tumor activity, then the administration of purified opsonic protein, which we have shown can activate the macrophage system, may significantly depress the growth and spread of experimental tumors. Thus, in vitro and in vivo experiments will be conducted to: quantify the tumor growth and metastatic spread in relationship to phagocytic activity, to compare the phagocytic activity, to compare the phagocytic activity of macrophages isolated at various post-transplantation intervals, and to delineate the temporal pattern of serum opsonic alterations during tumor growth. In addition, the interaction of opsonic protein with tumor cells and the value of opsonin therapy as a potential method to stimulate macrophages will be evaluated. Our recent ability to isolate, purify, and store opsonic protein from experimental animal and human serum provides us with an exciting opportunity to evaluate the critical role of this serum component in macrophage phagocytosis and host defense, which has been repeatedly implied by many basic and clinical studies. The present project should lead to a better understanding of the macrophage system as influenceed by malignant tumor growth, with subsequent extension within the clinical setting with regard to opsonin levels in patients with malignant disease.